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Questions for the Import Tolerance Meeting

Questions from the Advanced Notice of Proposed Rulemaking (ANPRM) for the VMAC Members

FDA is soliciting comment on all aspects of import tolerances and specifically on the following issues:

Issue 1: We set tolerances based upon the ADI and the relationship between the marker analyte and the total residue. To establish the tolerance, we consider conditions of use (including formulation, dose, and route of administration) and manufacturing features (including drug potency and purity). Regulatory agencies outside of the United States and international organizations may use different or additional factors to establish maximum residue levels (MRLs). The factors used by these regulatory agencies may include different edible tissue consumption factors or animal husbandry standards such as good agricultural practices. The effect of considering these factors may be a different tolerance value than the value established only on the basis of the human food safety data (as presented in section I.B of the ANPRM).

Question: There are different approaches that we could use to find a safe import tolerance. We could look at toxicity and residue data and build in a conservative safety factor. Alternatively, we could also review conditions of use such as good agricultural practices, route of administration, and dose, which may result in a different safety factor or factors. Additionally, we could consider manufacturing information such as that required for a domestic application, which also could result in a different safety factor or factors. Which approach is preferable?

Issue 2: The tolerance established by FDA for a new animal drug approved under section 512(b)(1) of the act is based on data submitted by the sponsor. These data are owned by the drug sponsor (pharmaceutical company, producer organization, etc.) that paid for the study and is accountable for the quality of the research. Each subsequent sponsor seeking approval of the drug under section 512(b)(1) of the act must submit similar human food safety data as required to support the tolerance for their product. Each new animal drug tolerance is established for each drug product, rather than for the drug substance/active ingredient. However, the ADAA allows for data for an import tolerance to include ``data submitted by the drug manufacturer to appropriate regulatory authorities in any country where the new animal drug is lawfully used or data available from a relevant international organization* * * .'' Any country wanting its producers to become eligible to export to the United States, could be a sponsor of an import tolerance.

Question: Only the drug marker residue for the drug substance, not the product formulation or the sponsor of the import tolerance, can be determined by the type of analytical method that is typically used to assay imports. Are there analytical techniques or other approaches that would allow us to determine whether a residue is due to use of the drug product for which the tolerance is approved?

Issue 3: We are considering how we should inform the public of the import tolerance process while also ensuring that we do not disclose trade secrets and confidential commercial information.

Questions:

(a) Should we disclose to the public that we are considering an import tolerance for a new animal drug?

(b) If so, when (e.g, upon request, upon filing)?

(c) How should we do so (e.g., Federal Register, Internet)?

(d) How much detail should we provide, keeping in mind that we cannot disclose trade secrets or confidential commercial information?

Issue 4: We are considering amending the regulations at 21 CFR 25.33 to allow a categorical exclusion for import tolerances under the National Environmental Policy Act, if there is information that shows that establishing import tolerances does not have a significant effect on the environment. We are seeking information on whether import tolerances will have a significant effect on the environment.

Issue 5: Please comment on any other aspects of import tolerances you wish to raise.